Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications

Accardo, Antonella; Morisco, Anna; Gianolio, Eliana; Tesauro, Diego; Mangiapia, Gaetano; Rădulescu, Aurel; Brandt, Astrid; Morelli, Giancarlo

doi:10.1002/psc.1308

Cited by 27 publications

(30 citation statements)

References 45 publications

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“…In this perspective, it does not surprise that the two peptides, containing the same aromatic portion, show a very close CAC value. However, it is also well-known that chelating agents such as DOTA and DTPA, can cause a steric and/or electrostatic hindrance, thus providing an increase of the CAC value1318. In our case, we can ascribe the low incidence of DOTA macrocycle on the fibrillary process in presence of the PEG chain; the latter being long enough to act as a spacer between the chelating agent and the aromatic framework.…”

Section: Resultsmentioning

confidence: 53%

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

Diaferia

Mercurio

Giannini

et al. 2016

Sci Rep

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Water soluble fibers of PEGylated tetra-phenylalanine (F4), chemically modified at the N-terminus with the DOTA chelating agent, have been proposed as innovative contrast agent (CA) in Magnetic Resonance Imaging (MRI) upon complexation of the gadolinium ion. An in-depth structural characterization of PEGylated F4-fibers, in presence (DOTA-L6-F4) and in absence of DOTA (L6-F4), is reported in solution and at the solid state, by a multiplicity of techniques including CD, FTIR, NMR, DLS, WAXS and SAXS. This study aims to better understand how the aggregation process influences the performance of nanostructures as MRI CAs. Critical aggregation concentrations for L6-F4 (43 μM) and DOTA-L6-F4 (75 μM) indicate that self-aggregation process occurs in the same concentration range, independently of the presence of the CA. The driving force for the aggregation is the π-stacking between the side chains of the aromatic framework. CD, FTIR and WAXS measurements indicate an antiparallel β-sheet organization of the monomers in the resulting fibers. Moreover, WAXS and FTIR experiments point out that in solution the nanomaterials retain the same morphology and monomer organizations of the solid state, although the addition of the DOTA chelating agent affects the size and the degree of order of the fibers.

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Section: Resultsmentioning

confidence: 53%

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

Diaferia

Mercurio

Giannini

et al. 2016

Sci Rep

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“…Moreover, the authors also studied liposomes prepared by co-aggregation of a synthetic amphiphilic monomer containing both the bioactive peptide and the chelating agent, with commercial phospholipids. In both cases, targeted nanocarriers engineered to conjugate imaging and therapeutic functions [20][21][22][23][24] were obtained for potential theranostic applications. Derivatized nanosystems, capable of diagnosis, drug delivery, and monitoring of therapeutic response, are expected to play a significant role in the dawning era of personalized medicine.…”

Section: Introductionmentioning

confidence: 99%

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

Accardo

Salsano

Morisco

et al. 2012

IJN

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Objectives: Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods: A new amphiphilic peptide derivative (MonY-BN) containing the BN(7-14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C 18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results: Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. Conclusion:The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy.

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“…23 Briefly, DO, PF127, and (C 18 ) 2 DTPA(Gd) were weighed and mixed in chloroform. The weight ratio of PF127 to DO was 15% (w/w).…”

Section: Preparation Of Nanostructures and Dls Characterizationmentioning

confidence: 99%

Diolein Based Nanostructures as Targeted Theranostics

Accardo¹,

Arena²,

Gianolio³

et al. 2016

j biomed nanotechnol

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Diolein based non-targeted theranostic nanoparticles (DO-NPs) containing 10%wt of the amphiphilic Gadolinium complex (C18)2DTPA(Gd), and targeted NPs, obtained by introducing growing amounts (3% wt, 6% wt or 10% wt) of (C18)2-Peg3000- FA in the sample composition, have been studied for their in vitro and in vivo properties. Cellular binding was studied by lCP-MS analysis of the Gadolinium content and by Surface Plasmon Resonance (SPR) assays. The best formulation in terms of selectivity towards IGROV-1 cells with respect to non-targeted DO-NPs, was that containing 3% (C18)2Peg3000- FA (P < 0.01). Cytotoxic studies and confocal microscopy analysis of IGROV-1 cells indicate high selective properties of the targeted doxorubicin (DOX) loaded NPs. Nanoparticles described here represent the first example in which a targeted carrier characterized by a stable foamy mesophase, provided by the Diolein component, combine the therapeutic effect due to the anticancer drug doxorubicin, with the imaging properties provided by paramagnetic gadolinium complexes for MRI. As evidenced by T(1w), and T(2w) MRI images and by the in vivo antitumor effect in IGROV-1 tumor-bearing mice, DO-NP3-FA/DOX provides very high therapeutic efficacy with a tumor growth regression of 80% and 50% higher as compared to the mice treated with saline solution and with Doxil, respectively.

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Nanoparticles containing octreotide peptides and gadolinium complexes for MRI applications

Cited by 27 publications

References 45 publications

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

Self-assembly of PEGylated tetra-phenylalanine derivatives: structural insights from solution and solid state studies

Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

Diolein Based Nanostructures as Targeted Theranostics

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